Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis

Abstract

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2–/–) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1–/– mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis.

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

“…Fibrosis is also a major pathological alteration in kidney injury [28]. In the present study, Masson staining revealed that the area of fibrosis in the kidney tissues increased Oxidative stress also exhibits an important influence on the progression of kidney injury [25].…”

“…Fibrosis is also a major pathological alteration in kidney injury [28]. In the present study, Masson staining revealed that the area of fibrosis in the kidney tissues increased significantly when challenged by ISO, while treatment with SOP apparently reversed this effect.…”

Editorial: Revisiting immunological roles for bone marrow stromal cell antigen-1; an entero-neuro-immune regulator

“…This Research Topic of Frontiers in Immunology will hopefully provide the reader with an overview of the role of BST-1/CD157 NAD+ metabolizing ectoenzyme in multiple physiological and pathological contexts emphasizing light and shadow. In recent years, burgeoning research on CD157 has broadened the horizon far beyond its role as an immunoregulator ( 22 ), raising new challenges. Among these, to understand the role of CD157 in the gut-brain axis influencing a variety of brain disorders is a top priority.…”